This application is for a competitive renewal of a multi-categorical General Clinical Research Center located[unreadable] at the Children's Hospital of Cincinnati. The Center provides inpatient, outpatient and scatter bed facilities[unreadable] within the Children's Hospital and a Core Laboratory supporting biochemical assays, body composition[unreadable] measurements, and behavioral studies at the Children's Hospital. A proposed satellite at the Veterans[unreadable] Administration Medical Center will help support studies in medically unstable adults who are not suitable to[unreadable] be studied at the Children's Hospital GCRC. Major areas of research include:[unreadable] 1. Cardiovascular disease: Studies are defining the potential role of differences in cholesterol absorption on[unreadable] cholesterol metabolism, the effects of disease states such as hypertension and chronic renal disease in[unreadable] children on cardiac and vascular function and anatomy.[unreadable] 2. Behavioral Interventions: Studies are exploring the effect of behavioral intervention in enhancing nutrient[unreadable] intake in cystic fibrosis, sickle cell disease, Crohn's Disease and others and assessing the impact of early[unreadable] traumatic brain injury on later neurocognitive development.[unreadable] 3. Cancer: Novel investigations are ongoing evaluating the effect of rapammune and similar compounds for[unreadable] the treatment of angiolipomata associated with tuberous sclerosis and lymphangioleiomyomatosis (LAMS)[unreadable] for whom no effective therapy other than surgery is available.[unreadable] 4. Obesity: Studies are defining the roles of changes in body composition in early life on the development of[unreadable] later obesity, examining racial disparities in body composition which occur during adolescence, and the[unreadable] impact of obesity on sleep disturbances and carbohydrate metabolism.[unreadable] 5. Gene Transfer: Gene transfer trials have been initiated at the GCRC to evaluate whether insertion of a[unreadable] wild type gene into the stem cells of patients with Fanconi Anemia will be safe and ultimately whether it will[unreadable] be efficacious in correcting their underlying bone marrow defects.[unreadable] 6. Diabetes Mellitus: The impact of Type 2 diabetes and obesity on cardiac and vascular structure and[unreadable] function in adolescents is being evaluated. The role of the insulinotropic Gl hormone glucagon-like peptide 1[unreadable] (GLP-1) in gastric emptying and insulin secretion in normal and Type 2 diabetics is being examined and its[unreadable] role in type 2 diabetes.[unreadable] 7. Inborn errors of bile acid metabolism: With a long track record of research and discovery of multiple[unreadable] enzymatic defects in the bile acid synthetic pathways, investigators at Children's Hospital continue to[unreadable] enhance understanding of these defects affecting infants and children with cholestasis and fat soluble[unreadable] vitamin deficiencies.